The ultimate objective of this research is to determine the biochemical basis of cell cycle-dependent variations in the cytotoxicity and mutagenicity of radiation and chemical agents, and to define the relationship of certain DNA repair processes to mammalian cell survival and mutagenesis. We propose to determine: a) the extent to which cell cycle-dependent variations in cell killing by mutagenic agents are paralleled by variations in induced mutation frequencies, b) whether cell killing and mutation induction by such agents display qualitatively similar dose-response kinetics, and c) the effects of specific DNA repair processes, dose-fractionation and inter-dose recovery time on the kinetics of repair and ultimate expression of potentially-lethal versus potentially-mutagenic lesions. A second major objective of this research is to isolate and characterize a broad spectrum of different mutagen-sensitive variants of CHO cells that could be used to investigate the molecular and genetic bases of DNA repair and somatic cell mutation.